Human dendritic cells transmit Enterovirus A71 to target cells independent of viral replication using heparan sulfates.

Enterovirus A71 (EV-A71) is a causative agent of life-threatening neurological diseases in young children. EV-A71 is highly infectious and it remains unclear how the virus disseminates from primary entry sites, the mucosa of the respiratory tract or the intestine, to secondary replication sites, skin or brain. A potential mechanism for viral dissemination is transmission by dendritic cells (DCs) which reside in the mucosa of the airway or gut and migrate to lymphoid tissues from which viral dissemination can further occur. Hence, we have investigated whether human monocyte-derived DCs are able to transmit EV-A71 to susceptible Rhabdomyosarcoma 99 (RD99) cell line. Transmission and infection were monitored by FACS and quantitative real-time PCR. DCs were not permissive to EV-A71 but DCs efficiently transmitted EV-A71 to RD99 cells and transmission was independent of viral replication, suggesting that EV-A71 transmission is independent of DC infection. Additionally, transmission was independent of DC-SIGN, whereas blocking binding of heparan sulfate (HS) abrogated transmission. This study provides evidence that DCs efficiently transmitted EV-A71 via a still unexplored trans-transmission route mediated by HS. These findings further elucidate EV-A71 pathogenesis and additional research might provide new treatment opportunities